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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Electrochemical nitrate reduction to ammonia offers an attractive solution to environmental sustainability and clean energy production. Here, the authors construct spin−polarized Fe₁−Ti pairs via manipulating oxygen vacancies on monolithic titanium electrode for highly efficient nitrate to ammonia conversion.

The magnetic character of the cuprates is suspected by many to be involved in the emergence of unconventional superconductivity. The discovery of a second distinct magnetic excitation in HgBa₂CuO₄ supports a multiband picture of the magnetic structure of these materials.

Here the authors report a genomic view of 3D chromatin reorganization following DNA damage. Movement of damaged DNA into nuclear domains, which is brought about by nuclear actin, favors error-free damage repair at the expense of rare chromosome rearrangements with oncogenic potential.

An antimatter hypernucleus formed by an anti-lambda hadron, an antiproton and two antineutrons was observed through its two-body decay after production in ultrarelativistic heavy-ion collisions.

Warming in climate simulations since about 1970, when aerosol cooling showed little variation, constrains the transient climate response to doubled atmospheric CO₂ levels to about 1.67 K, according to an analysis of this emergent constraint.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Measuring rhythm priors in 39 participant groups from 15 countries, the authors find that properties of rhythm representations are common across cultures, while variation from place to place related to local musical traditions exists.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Targeted protein degradation (TPD) has emerged as a new paradigm for modulating protein activity. Here, the authors develop bifunctional degraders combining a putative ligand of the autophagy-related LC3 protein with different protein targets, which direct proteins of interest to the proteasome by covalently targeting the DCAF11 E3 ligase substrate receptor.

Nano-environmental probes and advance imaging microscopy provide deep insight into protein phase separation and the interaction of condensates with membranes, revealing that wetting by condensates can modulate membrane lipid packing and hydration.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Ultra-low-temperature-actuated adsorption-driven chillers that rely on water as the cooling agent are desirable for energy-efficient and environmentally benign cooling devices. Here the authors show that the metal–organic framework of composition [Al(OH)(C₆H₂O₄S)] displays high water uptake capacity, high stability, and driving temperatures as low as 60 °C.

Space interferometry reveals the hidden and filamentary internal structure of the relativistic jet in 3C 279 at microarcsecond angular resolution. These details challenge previous assumptions on the morphology and radio variability of blazars.

Measurement of the bound-state β⁻ decay of ²⁰⁵Tl⁸¹⁺ gives a new, longer half-life, allowing for the calculation of accurate stellar ²⁰⁵Pb yields and the isolation time of the early Solar System.

Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Some cancer patients first present with metastases where the ___location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Developing efficient catalysts for acidic electrosynthesis of H₂O₂ is desirable, while most materials are compromised in acidic conditions. Here, the authors report that constructing amorphous Pt–Se shells on crystalline Pt cores can regulate the reaction pathway to efficiently produce H₂O₂ in acid.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

A probe for the ubiquitin-like protein Fubi led to the discovery of dual ubiquitin/Fubi C-terminal hydrolase activity in the deubiquitinase USP16 in addition to USP36, enabling structural characterization of this distinctive Ub/Ubl specificity, and revealed a synergistic role of USP16 in ribosomal protein maturation.

Biological light-driven ion pumps move ions against a concentration gradient to create a membrane potential, converting sunlight into an osmotic potential. Here, the authors make an artificial ion pump which drives ions thermodynamically uphill against a large concentration gradient upon illumination, which can be used for harvesting solar energy.

A self-assembled DNA structure is coupled to a nanopore and exhibits continuous rotation in the presence of nanoscale flows driven by electric fields or ionic gradients.

Solid-state lithium batteries typically utilize heterogeneous composite cathodes with conductive additives, which limit energy density and cycle life. Here the authors present a cathode material that exhibits efficient mixed conduction and near-zero volume change during cycling, thereby improving battery performance.

Skyrmions are objects with whirled magnetization protected by their topology that can be created by different means, however, without control of their position. Here, the authors present a method exploiting x-rays to create skyrmions at the beam position allowing for creation of artificial skyrmion lattices.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Carbon markets are key in climate strategies, but only 16% of carbon credits represent real emission reductions, based on a study of 2,346 projects. Reforms are needed to improve the effectiveness of carbon crediting mechanisms in addressing climate change.

The culture of genetically unmodified human naive embryonic stem cells in specific growth conditions gives rise to structures that recapitulate those of post-implantation human embryos up to 13–14 days after fertilization.

Despite its wide use in ageing research, the contribution of specific age-associated pathologies toC. elegansmortality is not well understood. Here the authors identify two types of death in worms, with either a swollen or a shrunken pharynx, that are differentially affected by age and mutations that extend worm lifespan.

There is crosstalk between the maintenance of DNA methylation and histone methylation. Here, the authors create an Uhrf1 knockin mouse model that abolishes the H3K9me2/3-binding activity of Uhrf1, and show that DNA maintenance methylation in mammals is largely independent of H3K9 methylation.

The EMDataResource Ligand Model Challenge aimed at assessing the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryo-EM maps determined at near-atomic resolution. This analysis presents the results and recommends best practices for assessing cryo-EM structures of liganded macromolecules.

Evidence for the presence of Homo during the Middle Pleistocene is limited in continental Southeast Asia. Here, the authors report a hominin molar from Tam Ngu Hao 2 (Cobra Cave), dated to 164–131 kyr. They use morphological and paleoproteomic analysis to show that it likely belonged to a female Denisovan.

A nanoscale DNA origami turbine is shown to perform mechanical rotation by directly harvesting transmembrane potential energy from an ion-concentration gradient across a solid-state nanopore. The direction of rotation is set by the designed chiral twist in the turbine’s blades.

Here, the authors built a non-redundant catalogue of nearly 1 billion putative small proteins from the global microbiome as a publicly-available resource, and highlight how some highly prevalent and evolutionarily conserved sequences lack functional annotation.

The Seebeck effect causes an electrical potential across a temperature gradient in a material, and is therefore useful for generating useful current from waste heat. Here, the authors show that the Seebeck effect can arise due to charge-carrier relaxation in addition to the conventional mechanism.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

The design and optimisation of 3D DNA-origami can be a barrier to rapid application. Here the authors design barrel structure of stacked 2D double helical rings with complex surface patterns.

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Reduced-dimensional halide perovskites are promising for light-emitting diodes but suffer from photo-degradation. Here Quan et al. identify the edge of the perovskite nanoplatelets as the degradation channels and use phosphine oxides to passivate the edges and boost device performance and lifetime.

The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.

The controlled growth of large-area single-crystalline 2D semiconductors remains a significant challenge for their electronic applications. Here, the authors report a quasi-equilibrium growth method to synthesize inch-scale monolayer α-In₂Se₃ with high mobility and ferroelectric field-effect transistor performance.